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Genetic bipolar

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https://www.readbyqxmd.com/read/28926153/comparative-and-population-genomics-landscape-of-phellinus-noxius-a-hypervariable-fungus-causing-root-rot-in-trees
#1
Chia-Lin Chung, Tracy J Lee, Mitsuteru Akiba, Hsin-Han Lee, Tzu-Hao Kuo, Dang Liu, Huei-Mien Ke, Toshiro Yokoi, Marylette B Roa, Meiyeh J Lu, Ya-Yun Chang, Pao-Jen Ann, Jyh-Nong Tsai, Chien-Yu Chen, Shean-Shong Tzean, Yuko Ota, Tsutomu Hattori, Norio Sahashi, Ruey-Fen Liou, Taisei Kikuchi, Isheng J Tsai
The order Hymenochaetales of white rot fungi contain some of the most aggressive wood decayers causing tree deaths around the world. Despite their ecological importance and the impact of diseases they cause, little is known about the evolution and transmission patterns of these pathogens. Here, we sequenced and undertook comparative genomics analyses of Hymenochaetales genomes using brown root rot fungus Phellinus noxius, wood-decomposing fungus Phellinus lamaensis, laminated root rot fungus Phellinus sulphurascens, and trunk pathogen Porodaedalea pini...
September 19, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28925351/parenting-practices-in-middle-childhood-mediate-the-relation-between-growing-up-with-a-parent-having-bipolar-disorder-and-offspring-psychopathology-from-childhood-into-early-adulthood
#2
Vanessa Iacono, Leah Beaulieu, Sheilagh Hodgins, Mark A Ellenbogen
The offspring of parents with bipolar disorder (OBD) are at high risk for developing mental disorders. In addition to genetic factors, environmental risk is purported to be associated with these negative outcomes. However, few studies have examined this relation. Using concurrent and longitudinal data, we examined if support, structure, and control provided by parents in middle childhood mediated the relation between having a parent with or without bipolar disorder, and offspring mental health. The sample included 145 offspring (77 OBD, 68 controls) aged 4 to 14 years and their parents...
September 19, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28924187/the-ipsych2012-case-cohort-sample-new-directions-for-unravelling-genetic-and-environmental-architectures-of-severe-mental-disorders
#3
C B Pedersen, J Bybjerg-Grauholm, M G Pedersen, J Grove, E Agerbo, M Bækvad-Hansen, J B Poulsen, C S Hansen, J J McGrath, T D Als, J I Goldstein, B M Neale, M J Daly, D M Hougaard, O Mors, M Nordentoft, A D Børglum, T Werge, P B Mortensen
The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28921675/altered-cav1-2-function-in-the-timothy-syndrome-mouse-model-produces-ascending-serotonergic-abnormalities
#4
Daniel G Ehlinger, Kathryn G Commons
Polymorphism in the gene CACNA1C, encoding the pore-forming subunit of Cav1.2 L-type calcium channels, has one of the strongest genetic linkages to schizophrenia, bipolar disorder, and major depressive disorder: psychopathologies in which serotonin signaling has been implicated. Additionally, a gain-of-function mutation in CACNA1C is responsible for the neurodevelopmental disorder Timothy Syndrome that presents with prominent behavioral features on the autism spectrum. Given an emerging role for serotonin in the etiology of autism spectrum disorders, we investigate the relationship between Cav1...
September 16, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28902457/the-role-of-clock-gene-in-psychiatric-disorders-evidence-from-human-and-animal-research
#5
REVIEW
Jaqueline B Schuch, Julia P Genro, Clarissa R Bastos, Gabriele Ghisleni, Luciana Tovo-Rodrigues
The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28902444/genomewide-association-studies-of-suicide-attempts-in-us-soldiers
#6
Murray B Stein, Erin B Ware, Colter Mitchell, Chia-Yen Chen, Susan Borja, Tianxi Cai, Catherine L Dempsey, Carol S Fullerton, Joel Gelernter, Steven G Heeringa, Sonia Jain, Ronald C Kessler, James A Naifeh, Matthew K Nock, Stephan Ripke, Xiaoying Sun, Jean C Beckham, Nathan A Kimbrel, Robert J Ursano, Jordan W Smoller
Suicide is a global public health problem with particular resonance for the US military. Genetic risk factors for suicidality are of interest as indicators of susceptibility and potential targets for intervention. We utilized population-based nonclinical cohorts of US military personnel (discovery: N = 473 cases and N = 9778 control subjects; replication: N = 135 cases and N = 6879 control subjects) and a clinical case-control sample of recent suicide attempters (N = 51 cases and N = 112 control subjects) to conduct GWAS of suicide attempts (SA)...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28900014/regulation-of-the-cell-cycle-and-centrosome-biology-by-deubiquitylases
#7
REVIEW
Sarah Darling, Andrew B Fielding, Dorota Sabat-Pośpiech, Ian A Prior, Judy M Coulson
Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. As potentially druggable enzymes, disease-associated DUBs are of increasing interest as pharmaceutical targets...
September 12, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28899920/the-trpm1-channel-is-required-for-development-of-the-rod-on-bipolar-cell-aii-amacrine-cell-pathway-in-the-retinal-circuit
#8
Takashi Kozuka, Taro Chaya, Fuminobu Tamalu, Mariko Shimada, Kayo Fujimaki-Aoba, Ryusuke Kuwahara, Shu-Ichi Watanabe, Takahisa Furukawa
Neurotransmission plays an essential role in neural circuit formation in the central nervous system. Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28895268/lithium-reduces-the-span-of-g-protein-activated-k-girk-channel-inhibition-in-hippocampal-neurons
#9
Nathan Dascal, Moran Rubinstein
OBJECTIVES: Lithium (Li(+) ) is one of the most widely used treatments for bipolar disorder (BD). However, the molecular and neuronal basis of BD, as well as the mechanisms of Li(+) actions are poorly understood. Cellular and biochemical studies identified G proteins as being among the cellular targets for Li(+) action, while genetic studies indicated an association with the KCNJ3 gene, which encodes the G protein-activated inwardly rectifying K(+) (GIRK) channels. GIRK channels regulate neuronal excitability by mediating the inhibitory effects of multiple neurotransmitters and contribute to the resting potassium conductance...
September 12, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28894008/genetic-disruption-of-ankyrin-g-in-adult-mouse-forebrain-causes-cortical-synapse-alteration-and-behavior-reminiscent-of-bipolar-disorder
#10
Shanshan Zhu, Zachary A Cordner, Jiali Xiong, Chi-Tso Chiu, Arabiye Artola, Yanning Zuo, Andrew D Nelson, Tae-Yeon Kim, Natalya Zaika, Brian M Woolums, Evan J Hess, Xiaofang Wang, De-Maw Chuang, Mikhail M Pletnikov, Paul M Jenkins, Kellie L Tamashiro, Christopher A Ross
Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28886448/exploring-hepsin-functional-genetic-variation-association-with-disease-specific-protein-expression-in-bipolar-disorder-applications-of-a-proteomic-informed-genomic-approach
#11
Malik Nassan, Yun-Fang Jia, Greg Jenkins, Colin Colby, Scott Feeder, Doo-Sup Choi, Marin Veldic, Susan L McElroy, David J Bond, Richard Weinshilboum, Joanna M Biernacka, Mark A Frye
In a prior discovery study, increased levels of serum Growth Differentiation Factor 15 (GDF15), Hepsin (HPN), and Matrix Metalloproteinase-7 (MMP7) were observed in bipolar depressed patients vs controls. This exploratory post-hoc analysis applied a proteomic-informed genomic research strategy to study the potential functional role of these proteins in bipolar disorder (BP). Utilizing the Genotype-Tissue Expression (GTEx) database to identify cis-acting blood expression quantitative trait loci (cis-eQTLs), five eQTL variants from the HPN gene were analyzed for association with BP cases using genotype data of cases from the discovery study (n = 58) versus healthy controls (n = 777)...
July 4, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28879196/assessment-of-whole-exome-sequence-data-in-attempted-suicide-within-a-bipolar-disorder-cohort
#12
Eric T Monson, Mehdi Pirooznia, Jennifer Parla, Melissa Kramer, Fernando S Goes, Marie E Gaine, Sophia C Gaynor, Kelly de Klerk, Dubravka Jancic, Rachel Karchin, W Richard McCombie, Peter P Zandi, James B Potash, Virginia L Willour
Suicidal behavior is a complex and devastating phenotype with a heritable component that has not been fully explained by existing common genetic variant analyses. This study represents the first large-scale DNA sequencing project designed to assess the role of rare functional genetic variation in suicidal behavior risk. To accomplish this, whole-exome sequencing data for ∼19,000 genes were generated for 387 bipolar disorder subjects with a history of suicide attempt and 631 bipolar disorder subjects with no prior suicide attempts...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28878340/the-pharmacogenomics-of-valproic-acid
#13
REVIEW
Miao-Miao Zhu, Hui-Lan Li, Li-Hong Shi, Xiao-Ping Chen, Jia Luo, Zan-Ling Zhang
Valproic acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. Adverse effects of valproic acid are rare, but hepatotoxicity is severe in particular in those younger than 2 years old and polytherapy. During valproic acid treatment, it is difficult for prescribers to predict its individual response. Recent advances in the field of pharmacogenomics have indicated variants of candidate genes that affect valproic acid efficacy and safety. In this review, a large number of candidate genes that influence valproic acid pharmacokinetics and pharmacodynamics are discussed, including metabolic enzymes, drug transporters, neurotransmitters and drug targets...
September 7, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28878002/combat-a-combined-association-test-for-genes-using-summary-statistics
#14
Minghui Wang, Jianfei Huang, Yiyuan Liu, Li Ma, James B Potash, Shizhong Han
Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Traditional analysis of GWAS typically examines one marker at a time, usually single nucleotide polymorphisms (SNPs), to identify individual variants associated with a disease. However, due to the small effect sizes of common variants, the power to detect individual risk variants is generally low. As a complementary approach to SNP-level analysis, a variety of gene-based association tests have been proposed...
September 6, 2017: Genetics
https://www.readbyqxmd.com/read/28874522/efficient-stimulus-secretion-coupling-at-ribbon-synapses-requires-rim-binding-protein-tethering-of-l-type-ca-2-channels
#15
Fujun Luo, Xinran Liu, Thomas C Südhof, Claudio Acuna
Fast neurotransmitter release from ribbon synapses via Ca(2+)-triggered exocytosis requires tight coupling of L-type Ca(2+) channels to release-ready synaptic vesicles at the presynaptic active zone, which is localized at the base of the ribbon. Here, we used genetic, electrophysiological, and ultrastructural analyses to probe the architecture of ribbon synapses by perturbing the function of RIM-binding proteins (RBPs) as central active-zone scaffolding molecules. We found that genetic deletion of RBP1 and RBP2 did not impair synapse ultrastructure of ribbon-type synapses formed between rod bipolar cells (RBCs) and amacrine type-2 (AII) cells in the mouse retina but dramatically reduced the density of presynaptic Ca(2+) channels, decreased and desynchronized evoked neurotransmitter release, and rendered evoked and spontaneous neurotransmitter release sensitive to the slow Ca(2+) buffer EGTA...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28869584/an-xqtl-map-integrates-the-genetic-architecture-of-the-human-brain-s-transcriptome-and-epigenome
#16
Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28859877/the-effect-of-stimulus-strength-on-binocular-rivalry-rate-in-healthy-individuals-implications-for-genetic-clinical-and-individual-differences-studies
#17
Phillip C F Law, Steven M Miller, Trung T Ngo
Binocular rivalry (BR) occurs when conflicting images concurrently presented to corresponding retinal locations of each eye stochastically alternate in perception. Anomalies of BR rate have been examined in a range of clinical psychiatric conditions. In particular, slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) to improve power in large-scale genome-wide association studies. Examining the validity of BR rate as a BD endophenotype however requires large-scale datasets (n=1000s to 10,000s), a standardized testing protocol, and optimization of stimulus parameters to maximize separation between BD and healthy groups...
August 28, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28856687/a-novel-relationship-for-schizophrenia-bipolar-and-major-depressive-disorder-part-3-evidence-from-chromosome-3-high-density-association-screen
#18
Xing Chen, Feng Long, Bin Cai, Xiaohong Chen, Gang Chen
Familial clustering of schizophrenia(SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was systematically reported (Aukes et al, Genet Med 2012, 14, 338-341) and convergent evidence from genetics, symptomatology and psychopharmacology imply that there are intrinsic connections between these three major psychiatric disorders, for example, any two or even three of these disorders could co-exist in some families. A total of 60, 838 single-nucleotide polymorphisms (SNPs)on chromosome 3 were genotyped by Affymetrix Genome-Wide Human SNP array 6...
August 30, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28852712/further-investigations-of-the-w-test-for-pairwise-epistasis-testing
#19
Richard Howey, Heather J Cordell
Background: In a recent paper, a novel W-test for pairwise epistasis testing was proposed that appeared, in computer simulations, to have higher power than competing alternatives. Application to genome-wide bipolar data detected significant epistasis between SNPs in genes of relevant biological function. Network analysis indicated that the implicated genes formed two separate interaction networks, each containing genes highly related to autism and neurodegenerative disorders. Methods: Here we investigate further the properties and performance of the W-test via theoretical evaluation, computer simulations and application to real data...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28837935/suicidal-behavior-in-the-context-of-disrupted-rhythmicity-in-bipolar-disorder-complementary-research-of-clock-genes-with-suicide-risks-factors-and-course-of-disease
#20
Joanna Pawlak, Aleksandra Szczepankiewicz, Pawel Kapelski, Aleksandra Rajewska-Rager, Agnieszka Slopien, Maria Skibinska, Piotr Czerski, Joanna Hauser, Monika Dmitrzak-Weglarz
Former findings indicate that suicidal behavior in bipolar disorder is associated with clock genes. Additionally, numerous non-genetic risk factors are potentially associated with suicidal behavior. Therefore, we conducted an analysis of the relationship between clock genes (as distal risk factors) with clinical characteristics and the course of bipolar disorder. We also tried to obtain a predictive model for suicide attempts based on clinical and genetic data. We found associations between selected polymorphisms and...
July 31, 2017: Psychiatry Research
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